Nuclear receptors, coactivators and chromatin: new approaches, new insights.

The actions of lipophilic hormones, including steroids, retinoids, thyroid hormone and vitamin D(3), are mediated through a conserved superfamily of nuclear receptor proteins that function as ligand-regulated, DNA-binding transcriptional activators in the chromatin environment of the nucleus. The ligand-dependent transcriptional activity of nuclear receptors is enhanced by various cofactors that remodel chromatin, acetylate nucleosomal histones and contact the basal transcriptional machinery. The current challenge is to understand the mechanistic details of how interactions among these factors enhance transcription of hormone-regulated genes assembled into chromatin. Current biochemical and cell-based methods are providing some important clues.